Juvenile Renal Dysplasia (JRD) is an important category of kidney disease in canines and is also sometimes referred to as juvenile nephropathy (Peeters D, Clercx C, Michiels L, Desmecht D, Snaps F, Henroteaux M, Day M J. 2000, Aust. Vet J. 78(3):162-165). Dysplasia is defined as abnormal growth or development of cells or organs. In the case of JRD, the kidney fails to develop properly during embryogenesis in the womb. At birth immature structures consisting of undifferentiated fetal cells or tissue types are found in the kidney. JRD in affected breeds share a common phenotype, characterized by immature glomeruli, and/or tubules and persistent mesenchyme, and defects in the renal cortex.
Many breeds of dogs are affected with JRD, and this has been documented in both veterinary textbooks (Kruger, J. M., Osborne, C. A., et al.: Congenital and Hereditary Disorders of the Kidney; Veterinary Pediatrics Dogs & Cats from Birth to Six Months, 2nd edition. (J. D. Hoskins, ed.) W.B.Saunders, Philadelphia, Pa., 1995: pp 401-406), as well as case reports and articles in the scientific literature (Abraham L A, Beck C, Slocombe R F Aust (2003) Vet J. 81(6):336-9; Peeters D, Clercx C, Michiels L, Desmecht D, Snaps F, Henroteaux M, Day M J. (2000). Aust Vet J. 78(3):162-165; Hoppe A, Karlstam E. (2000) J Small Anim Pract., 41(9):422-6; Olenick C L. (1999) Can Vet J.; 40(6):425-6; Schulze C, Meyer H P, Blok A L, Schipper K, van den Ingh T S. (1998) Vet Q. 20(4):146-8; Roels S, Schoofs S, Ducatelle R. (1997) Small Anim Pract. 38(3):115-8; Lobetti R G, Pearson J, Jimenez M. J Small Anim Pract., 37(11):552-5; Kerlin R L, Van Winkle T (1995) J. Vet Pathol. 32(3):327-9; Vilafranca M, Ferrer L. (1994) Vet Pathol. (3):375-7; Morton L D, Sanecki R K, Gordon D E, Sopiarz R L, Bell J S, Sakas P S. (1990) Vet Pathol. (6):455-8; Booth K. (1990) Vet Rec. 127(24):596-7; Nash A S, Creswick J A. (1988) Vet Rec. 123(25):654-5; Robinson W F, Huxtable C R, Gooding J R (1985) Aust Vet J. 62(4):109-12; Manderino D M, DeVries J G, Tamarkin J. (1984) Mod Vet Pract. 65(8):633-5; DiBartola S P, Chew D J, Boyce J T. (1983) J Am Vet Med. Assoc. 183(6):693-6; O'Brien T D, Osborne C A, Yano B L, Barnes D M. (1982) J Am Vet Med. Assoc. 180(6):658-64.)
Breeds most notably affected with JRD include Shih tzus, Lhasa apsos, and Soft Coated Wheaten Terriers and Miniature schnauzers. Other breeds reported in the scientific literature cited above include Golden retriever, Tibetan spaniel, Flat coated retriever, King Charles Cavalier spaniel, Standard Poodle, Cairn terrier, Tibetan terrier, Bull Mastiff, Boxers, Finnish Harriers, Rhodesian ridgeback, Flat coated retriever, Norwegian Elkhound, Bedlington Terriers, Chow Chows, Shetland sheepdogs Rottweilers, Alaskan Malamutes, Yorkshire terriers, Airedale Terriers, Irish Wolfhounds, Keeshonds, Old English sheepdogs, and Collies. There are probably others not yet reported in the veterinary literature as this disease has such a varied phenotype that it is most likely to be reported in breeds with a high frequency of these mutations.
The mode of inheritance of JRD has been widely debated, as this disease can present itself with a wide range of symptoms and pathological findings. Definitive diagnosis of JRD is done by a wedge biopsy that reveals dysplastic lesions, including abnormal ducts, and glomeruli. Individuals with an abnormal biopsy can be asymptomatic, showing no signs of the disease. On the other hand, affected animals may present with classic signs of chronic end stage renal failure or somewhere between these two extremes (see Bovee, 2003 The 28th Congress of the World Small Animal Veterinary Association Proceedings). Comprehensive data from biopsies from Shih Tzus presented by Bovee indicate that the mode of inheritance are most consistent with an autosomal dominance pattern with incomplete penetrance. This was largely supported by an outcross of a biopsy positive Shih Tzu with a normal poodle. The resultant progeny showed the presence of fetal glomeruli on biopsy.
The morphological features of JRD in dogs differ slightly from those in man (Picut C A, Lewis R M (1987) Vet Pathol. 24(2):156-63), and therefore selection of genes that are responsible for this disease is somewhat difficult from human disease, however, one possible gene described in mouse that causes renal dyplasia is the Cox2 gene (Ptgs2: Prostaglandin-endoperoxide synthase 2). While this gene is generally associated with biologic events such as injury, inflammation, and proliferation (Hla, T. and Neilson, K. (1993) Proc. Nat. Acad. Sci. 89: 7384-7388; Tazawa, R., Xu, X.-M., Wu, K. K., Wang, L.-H. (1994) Biochem. Biophys. Res. Commun. 203: 190-1999), the knockout mouse model shows abnormal kidney development, including but not limited to an abnormal renal cortex with small immature glomeruli, deteriorating tubules and glomerulosclerosis. Cox2 knockout mice also show increased blood urea nitrogen and circulation creatinine levels, consistent with impaired renal function. All homozygous adult mice showing renal disease are also subject to development of secondary pyelonephritis. The kidneys are generally small and pale in color. (Yu Y, Fan J, Chen X S, Wang D, Klein-Szanto A J, Campbell R L, FitzGerald G A, Funk C D. (2006) Nat. Med. June; 12(6):699-704; Dinchuk J E, Car B D, Focht R J, Johnston J J, Jaffee B D, Covington M B, Contel N R, Eng V M, Collins R J, Czerniak P M, et al. (1995) 1: Nature 378(6555):406-409). Other notable clinical abnormalities in knockout Cox2 mice include, decreased litter size, reduced fertility in females, and patent ductus arteriosis.